Is azithromycin (Zithromax) safe to use during pregnancy at 25 weeks of gestation?

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Last updated: November 29, 2025View editorial policy

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Azithromycin Safety at 25 Weeks Gestation

Yes, azithromycin is safe to use at 25 weeks of pregnancy and is classified as FDA Pregnancy Category B, with CDC guidelines recommending it as a preferred macrolide antibiotic during pregnancy. 1, 2, 3

FDA Classification and Safety Profile

  • Azithromycin is designated as FDA Pregnancy Category B, meaning animal reproduction studies have shown no evidence of harm to the fetus at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500 mg, though adequate and well-controlled studies in pregnant women are lacking. 3

  • The CDC specifically identifies azithromycin as the preferred macrolide antibiotic during pregnancy based on animal studies and clinical experience showing its safety profile. 2

  • No conclusive evidence exists that azithromycin use during pregnancy causes adverse fetal outcomes, according to CDC guidelines. 2

Clinical Evidence Supporting Safety

  • A prospective cohort study of 123 pregnant women exposed to azithromycin (71.6% during first trimester) found no statistically significant increase in major malformations compared to disease-matched controls (3.4% vs 2.3%) or non-teratogen controls (3.4%), which is within the baseline rate of 1-3%. 4

  • Pharmacokinetic studies in pregnant women at various gestational ages demonstrate that azithromycin is well-tolerated, with pregnancy causing an 86% increase in volume of distribution but no significant change in drug exposure (AUC), and no dose adjustment is needed. 5

  • Animal studies in sheep at 80 days gestation (equivalent to second trimester) showed substantial fetal tissue uptake with repeated maternal intravenous dosing, with no evidence of fetal injury, hepatotoxicity, or inflammatory markers. 6

Approved Indications During Pregnancy

  • Chlamydial infections: CDC recommends azithromycin 1g orally as a single dose as first-line treatment during pregnancy due to superior efficacy, safety profile, and excellent compliance. 7

  • MAC prophylaxis in HIV-infected pregnant women: Azithromycin is specifically recommended as the drug of choice. 2

  • Pertussis treatment and prophylaxis: Azithromycin is the preferred macrolide, particularly for infants <1 month and by extension for pregnant women. 1

Important Clinical Caveats

  • Do not confuse with clarithromycin, which has been demonstrated to be a teratogen in animals and should be used with caution during pregnancy. 2

  • While a 2022 review noted conflicting results regarding risks of spontaneous miscarriage, congenital malformations, and preterm birth in some studies, the authors concluded there is no conclusive evidence supporting that azithromycin causes adverse offspring outcomes. 8

  • Azithromycin should only be used when clinically indicated during pregnancy, ensuring benefits outweigh potential risks. 3, 8

  • The drug is excreted in breast milk, so caution should be exercised if breastfeeding, though this is not relevant at 25 weeks gestation. 3

Contraindications to Note

  • For syphilis treatment in pregnancy, azithromycin has insufficient efficacy data and should not be used; penicillin remains the only proven effective treatment. 1

  • Azithromycin is inappropriate for urinary tract infections as it lacks activity against gram-negative uropathogens that cause UTIs. 9

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Azithromycin Safety in First Trimester of Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Pharmacokinetic properties of azithromycin in pregnancy.

Antimicrobial agents and chemotherapy, 2010

Guideline

Treatment of Chlamydia in Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Azithromycin in Pregnancy for UTIs

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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